Skip to main content

Sequence and Structure Analysis of Noncoding RNAs

  • Protocol
  • First Online:
Data Mining Techniques for the Life Sciences

Part of the book series: Methods in Molecular Biology ((MIMB,volume 609))

Abstract

Noncoding RNAs (ncRNAs) are increasingly recognized as important functional molecules in the cell. Here we give a short overview of fundamental computational techniques to analyze ncRNAs that can help us better understand their function. Topics covered include prediction of secondary structure from the primary sequence, prediction of consensus structures for homologous sequences, search for homologous sequences in databases using sequence and structure comparisons, annotation of tRNAs, rRNAs, snoRNAs, and microRNAs, de novo prediction of novel ncRNAs, and prediction of RNA/RNA interactions including miRNA target prediction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bompfünewerer, A., Flamm, C., Fried, C., Fritzsch, G., Hofacker, I., Lehmann, J., Missal, K., Mosig, A., Müller, B., Prohaska, S., Stadler, B., Stadler, P., Tanzer, A., Washietl, S., Witwer, C. (2005) Evolutionary patterns of non-coding RNAs. Theor Biosci 123, 301–369.

    Article  Google Scholar 

  2. Hofacker, I. L., Fontana, W., Stadler, P. F., Bonhoeffer, L. S., Tacker, M., Schuster, P. (1994) Fast folding and comparison of RNA secondary structures. Monatsh Chem 125, 167–188.

    Article  CAS  Google Scholar 

  3. Knudsen, B., Hein, J. (2003) Pfold: RNA secondary structure prediction using stochastic context-free grammars. Nucleic Acids Res 31, 3423–3428.

    Article  CAS  PubMed  Google Scholar 

  4. Washietl, S., Hofacker, I. L., Stadler, P. F. (2005) Fast and reliable prediction of noncoding RNAs. Proc Natl Acad Sci USA 102, 2454–2459.

    Article  CAS  PubMed  Google Scholar 

  5. Rivas, E., Eddy, S. R. (2001) Noncoding RNA gene detection using comparative sequence analysis. BMC Bioinformatics 2, 8–8.

    Article  CAS  PubMed  Google Scholar 

  6. Yao, Z., Weinberg, Z., Ruzzo, W. L. (2006) CMfinder – a covariance model based RNA motif finding algorithm. Bioinformatics 22, 445–452.

    Article  CAS  PubMed  Google Scholar 

  7. Eddy, S. R., Durbin, R. (1994) RNA sequence analysis using covariance models. Nucleic Acids Res 22, 2079–2088.

    Article  CAS  PubMed  Google Scholar 

  8. Hofacker, I. L. (2007) RNA consensus structure prediction with RNAalifold. Methods Mol Biol 395, 527–544.

    CAS  PubMed  Google Scholar 

  9. Washietl, S., Hofacker, I. L. (2004) Consensus folding of aligned sequences as a new measure for the detection of functional RNAs by comparative genomics. J Mol Biol 342, 19–30.

    Article  CAS  PubMed  Google Scholar 

  10. Clote, P., Ferre, F., Kranakis, E., Krizanc, D. (2005) Structural RNA has lower folding energy than random RNA of the same dinucleotide frequency. RNA 11, 578–591.

    Article  CAS  PubMed  Google Scholar 

  11. Freyhult, E. K., Bollback, J. P., Gardner, P. P. (2007) Exploring genomic dark matter: a critical assessment of the performance of homology search methods on noncoding RNA. Genome Res 17, 117–125.

    Article  CAS  PubMed  Google Scholar 

  12. Griffiths-Jones, S., Moxon, S., Marshall, M., Khanna, A., Eddy, S. R., Bateman, A. (2005) Rfam: annotating non-coding RNAs in complete genomes. Nucleic Acids Res 33, D121–D124.

    Article  CAS  PubMed  Google Scholar 

  13. Lowe, T. M., Eddy, S. R. (1997) tRNAscan-SE: a program for improved detection of transfer RNA genes in genomic sequence. Nucleic Acids Res 25, 955–964.

    Article  CAS  PubMed  Google Scholar 

  14. Lagesen, K., Hallin, P., Rodland, E. A., Staerfeldt, H. H., Rognes, T., Ussery, D. W. (2007) RNAmmer: consistent and rapid annotation of ribosomal RNA genes. Nucleic Acids Res 35, 3100–3108.

    Article  CAS  PubMed  Google Scholar 

  15. Lowe, T. M., Eddy, S. R. (1999) A computational screen for methylation guide snoRNAs in yeast. Science 283, 1168–1171.

    Article  CAS  PubMed  Google Scholar 

  16. Schattner, P., Decatur, W. A., Davis, C. A., , Fournier, M. J., Lowe, T. M. (2004) Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome. Nucleic Acids Res 32, 4281–4296.

    Article  CAS  PubMed  Google Scholar 

  17. Hertel, J., Hofacker, I. L., Stadler, P. F. (2008) SnoReport: computational identification of snoRNAs with unknown targets. Bioinformatics 24, 158–164.

    Article  CAS  PubMed  Google Scholar 

  18. Laslett, D., Canback, B., Andersson, S. (2002) BRUCE: a program for the detection of transfer-messenger RNA genes in nucleotide sequences. Nucleic Acids Res 30, 3449–3453.

    Article  CAS  PubMed  Google Scholar 

  19. Regalia, M., Rosenblad, M. A., Samuelsson, T. (2002) Prediction of signal recognition particle RNA genes. Nucleic Acids Res 30, 3368–3377.

    Article  CAS  PubMed  Google Scholar 

  20. Lim, L. P., Glasner, M. E., Yekta, S., Burge, C. B., Bartel, D. P. (2003) Vertebrate microRNA genes. Science 299, 1540.

    Article  CAS  PubMed  Google Scholar 

  21. Huang, T. H., Fan, B., Rothschild, M. F., Hu, Z. L., Li, K., Zhao, S. H. (2007) MiRFinder: an improved approach and software implementation for genome-wide fast microRNA precursor scans. BMC Bioinformatics 8, 341.

    Article  PubMed  Google Scholar 

  22. Ng, K. L., Mishra, S. K. (2007) De novo SVM classification of precursor microRNAs from genomic pseudo hairpins using global and intrinsic folding measures. Bioinformatics 23, 1321–1330.

    Article  CAS  PubMed  Google Scholar 

  23. Jiang, P., Wu, H., Wang, W., Ma, W., Sun, X., Lu, Z. (2007) MiPred: classification of real and pseudo microRNA precursors using random forest prediction model with combined features. Nucleic Acids Res 35, W339–W344.

    Article  PubMed  Google Scholar 

  24. Xue, C., Li, F., He, T., Liu, G. P., Li, Y., Zhang, X. (2005) Classification of real and pseudo microRNA precursors using local structure-sequence features and support vector machine. BMC Bioinformatics 6, 310.

    Article  PubMed  Google Scholar 

  25. Nam, J. W., Shin, K. R., Han, J., Lee, Y., Kim, V. N., Zhang, B. T. (2005) Human microRNA prediction through a probabilistic co-learning model of sequence and structure. Nucleic Acids Res 33, 3570–3581.

    Article  CAS  PubMed  Google Scholar 

  26. Yousef, M., Nebozhyn, M., Shatkay, H., Kanterakis, S., Showe, L. C., Showe, M. K. (2006) Combining multi-species genomic data for microRNA identification using a Naive Bayes classifier. Bioinformatics 22, 1325–1334.

    Article  CAS  PubMed  Google Scholar 

  27. Hertel, J., Stadler, P. F. (2006) Hairpins in a Haystack: recognizing microRNA precursors in comparative genomics data. Bioinformatics 22, e197–e202.

    Article  CAS  PubMed  Google Scholar 

  28. Terai, G., Komori, T., Asai, K., Kin, T. (2007) miRRim: a novel system to find conserved miRNAs with high sensitivity and specificity. RNA 13, 2081–2090.

    Article  CAS  PubMed  Google Scholar 

  29. Dezulian, T., Remmert, M., Palatnik, J. F., Weigel, D., Huson, D. H. (2006) Identification of plant microRNA homologs. Bioinformatics 22, 359–360.

    Article  CAS  PubMed  Google Scholar 

  30. Wang, X., Zhang, J., Li, F., Gu, J., He, T., Zhang, X., Li, Y. (2005) MicroRNA identification based on sequence and structure alignment. Bioinformatics 21, 3610–3614.

    Article  CAS  PubMed  Google Scholar 

  31. Grad, Y., Aach, J., Hayes, G. D., Reinhart, B. J., Church, G. M., Ruvkun, G., Kim, J. (2003) Computational and experimental identification of C. elegans microRNAs. Mol Cell 11, 1253–1263.

    Article  CAS  PubMed  Google Scholar 

  32. Ritchie, W., Legendre, M., Gautheret, D. (2007) RNA stem-loops: to be or not to be cleaved by RNAse III. RNA 13, 457–462.

    Article  CAS  PubMed  Google Scholar 

  33. Adai, A., Johnson, C., Mlotshwa, S., Archer-Evans, S., Manocha, V., Vance, V., Sundaresan, V. (2005) Computational prediction of miRNAs in Arabidopsis thaliana. Genome Res 15, 78–91.

    Article  CAS  PubMed  Google Scholar 

  34. Helvik, S. A., and Saetrom, P. (2007) Reliable prediction of Drosha processing sites improves microRNA gene prediction. Bioinformatics 23, 142–149.

    Article  CAS  PubMed  Google Scholar 

  35. Bonnet, E., Wuyts, J., Rouze, P., Van de Peer, Y. (2004) Detection of 91 potential conserved plant microRNAs in Arabidopsis thaliana and Oryza sativa identifies important target genes. Proc Natl Acad Sci USA 101, 11511–11516.

    Article  CAS  PubMed  Google Scholar 

  36. Vogel, J., Wagner, E. G. (2007) Target identification of small noncoding RNAs in bacteria. Curr Opin Microbiol 10, 262–270.

    Article  CAS  PubMed  Google Scholar 

  37. Maziere, P., Enright, A. J. (2007) Prediction of microRNA targets. Drug Discov Today 12, 452–458.

    Article  CAS  PubMed  Google Scholar 

  38. Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., Segal, E. (2007) The role of site accessibility in microRNA target recognition. Nat Genet 39, 1278–1284.

    Article  CAS  PubMed  Google Scholar 

  39. Long, D., Chan, C. Y., Ding, Y. (2008) Analysis of microRNA-target interactions by a target structure based hybridization model. Pac Symp Biocomput 13, 64–74.

    Google Scholar 

  40. Lewis, B. P., Burge, C. B., Bartel, D. P. (2005) Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120, 15–20.

    Article  CAS  PubMed  Google Scholar 

  41. Enright, A. J., John, B., Gaul, U., Tuschl, T., Sander, C., Marks, D. S. (2003) MicroRNA targets in Drosophila. Genome Biol 5, R1.

    Article  PubMed  Google Scholar 

  42. Krek, A., Grun, D., Poy, M. N., Wolf, R., Rosenberg, L., Epstein, E. J., MacMenamin, P., da Piedade, I., Gunsalus, K. C., Stoffel, M., Rajewsky, N. (2005) Combinatorial microRNA target predictions. Nat Genet 37, 495–500.

    Article  CAS  PubMed  Google Scholar 

  43. Miranda, K. C., Huynh, T., Tay, Y., Ang, Y. S., Tam, W. L., Thomson, A. M., Lim, B., Rigoutsos, I. (2006) A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes. Cell 126, 1203–1217.

    Article  CAS  PubMed  Google Scholar 

  44. Kiriakidou, M., Nelson, P. T., Kouranov, A., Fitziev, P., Bouyioukos, C., Mourelatos, Z., Hatzigeorgiou, A. (2004) A combined computational-experimental approach predicts human microRNA targets. Genes Dev 18, 1165–1178.

    Article  CAS  PubMed  Google Scholar 

  45. Kim, S. K., Nam, J. W., Rhee, J. K., Lee, W. J., Zhang, B. T. (2006) miTarget: microRNA target gene prediction using a support vector machine. BMC Bioinformatics 7, 411.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The author thanks Ivo L. Hofacker and Paul P. Gardner for useful discussions and Gregory Jordan and Stephan Bernhart for comments on the manuscript. This work was supported by Austrian GEN–AU project “noncoding RNA.”

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Washietl, S. (2010). Sequence and Structure Analysis of Noncoding RNAs. In: Carugo, O., Eisenhaber, F. (eds) Data Mining Techniques for the Life Sciences. Methods in Molecular Biology, vol 609. Humana Press. https://doi.org/10.1007/978-1-60327-241-4_17

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-241-4_17

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60327-240-7

  • Online ISBN: 978-1-60327-241-4

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics